The invention relates to a glass multiple well assay plate for applications in biological or chemical assays.
The relationship between structure and function of molecules is a fundamental issue in the study of biological and other chemical based systems. Structure-function relationships are important in understanding, for example, the function of enzymes, cellular communication, and cellular control and feedback mechanisms. Certain macromolecules are known to interact and bind to other molecules having a specific three dimensional spacial and electronic distribution. Any macromolecule having such specificity can be considered a receptor, whether the macromolecule is an enzyme, a protein, a glycoprotein, an antibody, an oligonucleotide sequence of DNA, RNA or the like. The various molecules to which receptors bind are known as ligands.
Pharmaceutical drug discovery is one type of research that relies on the study of structure-function relationships. Much contemporary drug discovery involves discovering novel ligands with desirable patterns of specificity for biologically important receptors. Thus, the time to bring new drugs to market could be greatly reduced through the use of methods and apparatus which allow rapid generation and screening of large numbers of ligands.
A common way to generate such ligands is to synthesize libraries of ligands on solid phase resins. Since the introduction of solid phase synthesis methods for peptides, oligonucleotides, and other polynucleotides, new methods employing solid phase strategies have been developed that are capable of generating thousands, and in some cases millions of individual peptide or nucleic acid polymers using automated or manual techniques. These synthesis strategies, which generate families or libraries of compounds are generally referred to as xe2x80x9ccombinatorial chemistryxe2x80x9d or xe2x80x9ccombinatorial synthesisxe2x80x9d strategies.
The current storage format for compound libraries is a 96 well format well plate typically made from polypropylene and having rubber stopper sheets or hot seal covers. Certain processes and chemistries require that chemical reagents (which may be reactants, solvents, or reactants dissolved in solvents) be kept under inert or anhydrous conditions to prevent reactive groups from reacting with molecular oxygen, water vapor, or other agents. Examples of moisture sensitive chemistries include peptide chemistry, nucleic acid chemistry, organometallic, heterocyclic, and chemistries commonly used to construct combinatorial chemistry libraries. The solvent used for storage of synthesized chemicals is typically dimethylsulfoxide (DMSO).
Storage plates made from polymers have the disadvantage of being incapable of withstanding the extreme temperature variations that are sometimes required in combinatorial chemistry reactions and storage (between xe2x88x9220xc2x0 and 370xc2x0 C.).
Creating a multiwell plate from glass is a solution to this and other problems that are inherent in using polymers, such as sample interaction with the base polymer making up the plate. Glass, however cannot be injection molded and it is extremely difficult to press a gob of glass into a 96 well plate mold. One method currently used in producing a multiwell plate from glass involves a boring process. In this process, slabs of borosilicate glass conforming to the industry standard 96 well plate footprint are machined such that 96 individual wells are bored into the slab. This approach however is extremely costly.
Another method of making glass well plates involves vacuum thermoforming. By this method, small plates are produced from glass by vacuum thermoforming a thin glass sheet, as described in commonly assigned French patent application 96-13530. This technique offers well volumes of anywhere from 200xcexcml volume capacity per well. While these volumes may be convenient for high-throughput screening bioassay applications aimed at sample and reagent conservation, they are probably too small for chemical synthesis in organic solvent, the storage of drugs or drug candidates in organic solvent or long term storage where closure is required.
Further, a need for plates having wells having opaque side walls and transparent bottoms has emerged. The transparent well bottoms allow for analytical detection of chemiluminescent, phosphorescent, and luminescent sample tags as used in many chemical and biological tests, experiments and assays. The opaque sidewalls meanwhile serve to prevent crosstalk between neighboring wells and thereby help eliminate any false readings. Plastic plates having wells having opaque side walls and transparent bottoms are commonly sold by many companies including Corning Incorporated and Packard.
It is therefore an object of the present invention to provide a multiwell plate that can be manufactured from glass in a cost effective way. Further, it is an object to provide a method of making a glass multiwell plate that can produce varied and unique well designs. It is another object to provide a glass multiwell plate having a high density of wells per unit plate. It is yet another object of the present invention to provide a multiwell plate than can withstand great variations in temperature. It is another object of the present invention to provide a method for making a plate with wells having transparent bottoms and opaque sidewalls. Further it is an object of the present invention to provide a plate having wells having opaque sidewalls and a transparent bottom at least a portion of the plate being composed of glass. It is yet another object of the present invention to provide a multiwell plate with a depth/well diameter ratio far greater than presently available. A further object is to provide a plate that enables increased sensitivity of light detection from its wells.
The present invention relates to a method of making a multiwell plate for use in biological and chemical assays, experimentation and storage. The method comprises the steps of extruding a powdered glass/binder batch mixture through a honeycomb die thereby creating a preform block, sintering the extruded preform, slicing the sintered block into sections, and binding the sliced sections to a substantially flat bottom piece made of either glass or an organic polymer. Alternatively, a polymer may be extruded through a die, slided, and combined with a substantially flat bottom piece made of either glass or an organic polymer.